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Journal of Alzheimer's Disease : JAD 2024Accumulating evidence has demonstrated that hyperglycemia is a possible risk factor for mild cognitive impairment or Alzheimer's disease. Diabetic retinopathy (DR) has...
BACKGROUND
Accumulating evidence has demonstrated that hyperglycemia is a possible risk factor for mild cognitive impairment or Alzheimer's disease. Diabetic retinopathy (DR) has been identified as a risk factor for dementia in patients with diabetes.
OBJECTIVE
This study aimed to investigate the causal relationships between DR and brain structure, cognitive function, and dementia.
METHODS
We performed bidirectional two-sample Mendelian randomization for DR, brain structure, cognitive function, and dementia using the inverse-variance weighted method.
RESULTS
Inverse-variance weighted analysis showed the association of DR with vascular dementia (OR = 1.68, 95% CI: 1.01-2.82), and dementia was significantly associated with the increased risk of non-proliferative DR (NPDR) (OR = 1.76, 95% CI: 1.04-2.98). Furthermore, better cognitive performance was significantly associated with a reduced risk of NPDR (OR = 0.85, 95% CI: 0.74-0.98). No association was observed between DR and brain structure.
CONCLUSIONS
These findings suggest that the association of DR with vascular dementia. The reciprocal effect of cognitive performance and dementia on NPDR risk highlights the potential benefits of dementia prevention for reducing the burden of DR.
Topics: Humans; Diabetic Retinopathy; Dementia, Vascular; Mendelian Randomization Analysis; Brain; Cognition; Genome-Wide Association Study; Diabetes Mellitus
PubMed: 38217603
DOI: 10.3233/JAD-231022 -
Skin Research and Technology : Official... Nov 2023Structural abnormalities in the brain of patients with atopic dermatitis (AD) have been reported; however, the cause has not been determined yet. Herein, we used... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Structural abnormalities in the brain of patients with atopic dermatitis (AD) have been reported; however, the cause has not been determined yet. Herein, we used Mendelian randomization (MR) to reveal the causal effect of AD on brain structure.
METHODS
This study utilized summary statistics from genome-wide association studies (GWASs) to investigate a collection of cerebral structural measures, encompassing cortical thickness (CT), cortical surface area (CA), and subcortical volumes in T1 images. A comprehensive GWAS meta-analysis identified a total of 20 independent single nucleotide polymorphisms linked to AD, surpassing the genome-wide significance threshold (p < 5 × 10⁻⁸). MR estimates were aggregated through the application of the inverse variance weighted method. Additional complementary analyses (i.e., MR-Egger and weighted median approaches) were conducted to further assess the robustness of the obtained results. Sensitivity analysis and multivariate MR (MVMR) while adjusting for brain structural changes risk factors (i.e., depression and anxiety) were performed to assess the reliability and stability of observed causality.
RESULTS
Genetically determined AD exhibited a causal link with reduced caudate volumes (IVW-MR: β = -0.186, p = 0.001, p-corrected = 0.009). Furthermore, we identified potential causal associations between AD and reduced CT in the cingulate region (posterior cingulate, IVW-MR: β = -0.065, p = 0.018, p-corrected = 0.551; isthmus cingulate, IVW-MR: β = -0.086, p = 0.003, p-corrected = 0.188), as well as abnormal cortical surface area (CA) in the supramarginal (IVW-MR: β = -0.047, p = 0.044, p-corrected = 0.714) and isthmus cingulate (IVW-MR: β = 0.053, p = 0.018, p-corrected = 0.714). Additional supplementary analyses yielded consistent outcomes. There was no evidence of horizontal pleiotropy. MVMR analysis showed that the causal effects of AD on abnormal brain structure remained significant while adjusting for depression and anxiety.
CONCLUSION
This MR study provided suggestive evidence that decreased caudate nucleus, posterior cingulate cortex, isthmus cingulate cortex and supramarginal gyrus are suggestively associated with higher AD risk. Future investigation into the brain regions is recommended, which helps to clarify the underlying mechanisms and point to new therapies against AD.
Topics: Humans; Dermatitis, Atopic; Genome-Wide Association Study; Mendelian Randomization Analysis; Reproducibility of Results; Brain
PubMed: 38009032
DOI: 10.1111/srt.13515 -
Psychiatry Research. Neuroimaging Dec 2023The structural neural correlates underlying youth nonsuicidal self-injury (NSSI) warrant further exploration. Few studies have explored the association between NSSI and...
The structural neural correlates underlying youth nonsuicidal self-injury (NSSI) warrant further exploration. Few studies have explored the association between NSSI and brain structure in adolescence, and no studies have investigated differences in the relation between age and brain structure in youth with NSSI. This preliminary investigation examined associations between NSSI history, age, and cortical structure using magnetic resonance imaging in adolescent girls (=100, =13.4 years) at increased risk for psychopathology. We conducted whole-brain analyses to investigate the associations between age and cortical structure, NSSI history and cortical structure, and NSSI history as a moderator of the association between age and cortical structure. Results suggested that age was associated with less cortical thickness and surface area in the left and right prefrontal, temporal, and parietal cortex. NSSI history was associated with less left insula and left inferior parietal cortex cortical surface area. Among adolescents with NSSI history, older age predicted greater left inferior parietal cortex surface area and was not associated with left precentral cortex surface area. Among adolescents without NSSI history, older age predicted smaller surface areas as expected with the typical trajectory of neurodevelopment. Overall, our results suggest differences in cortical surface area development in adolescents with NSSI history.
Topics: Female; Humans; Adolescent; Self-Injurious Behavior; Brain; Adolescent Behavior; Cerebral Cortex; Magnetic Resonance Imaging
PubMed: 38456014
DOI: 10.1016/j.pscychresns.2023.111725 -
Frontiers in Neurology 2024Dysregulation of circulating metabolites may affect brain function and cognition, associated with alterations in the cerebral cortex architecture. However, the exact...
BACKGROUND
Dysregulation of circulating metabolites may affect brain function and cognition, associated with alterations in the cerebral cortex architecture. However, the exact cause remains unclear. This study aimed to determine the causal effect of circulating metabolites on the cerebral cortex architecture.
METHODS
This study utilized retrieved data from genome-wide association studies to investigate the relationship between blood metabolites and cortical architecture. A total of 1,091 metabolites and 309 metabolite ratios were used for exposure. The brain cortex surface area and cortex thickness were selected as the primary outcomes in this study. In this study, the inverse variance weighting method was used as the main analytical method, complemented by sensitivity analyses that were more robust to pleiotropy. Furthermore, metabolic pathway analysis was performed via MetaboAnalyst 6.0. Finally, reverse Mendelian randomization (MR) analysis was conducted to assess the potential for reverse causation.
RESULTS
After correcting for the false discovery rate (FDR), we identified 37 metabolites and 9 metabolite ratios that showed significant causal associations with cortical structures. Among these, Oxalate was found to be most strongly associated with cortical surface area (: 2387.532, 95% CI 756.570-4018.495, = 0.037), while Tyrosine was most correlated with cortical thickness (: -0.015, 95% CI -0.005 to -0.025, = 0.025). Furthermore, pathway analysis based on metabolites identified six significant metabolic pathways associated with cortical structures and 13 significant metabolic pathways based on metabolite ratios.
CONCLUSION
The identified metabolites and relevant metabolic pathways reveal potential therapeutic pathways for reducing the risk of neurodegenerative diseases. These findings will help guide health policies and clinical practice in treating neurodegenerative diseases.
PubMed: 38784905
DOI: 10.3389/fneur.2024.1386844 -
JAMA Network Open Feb 2024Weight loss induced by bariatric surgery (BS) is associated with improved cognition and changed brain structure; however, previous studies on the association have used...
IMPORTANCE
Weight loss induced by bariatric surgery (BS) is associated with improved cognition and changed brain structure; however, previous studies on the association have used small cohorts and short follow-up periods, making it difficult to determine long-term neurological outcomes associated with BS.
OBJECTIVE
To investigate long-term associations of weight loss after BS with cognition and brain structure and perfusion.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study included participants from the Bariatric Surgery Rijnstate and Radboudumc Neuroimaging and Cognition in Obesity study. Data from participants with severe obesity (body mass index [BMI; calculated as weight in kilograms divided by height in meters squared] >40, or BMI >35 with comorbidities) eligible for Roux-en-Y gastric bypass and aged 35 to 55 years were enrolled from a hospital specialized in BS (Rijnstate Hospital, Arnhem, the Netherlands). Participants were recruited between September 2018 and December 2020 with follow-up till March 2023. Data were collected before BS and at 6 and 24 months after BS. Data were analyzed from March to November 2023.
EXPOSURE
Roux-en-Y gastric bypass.
MAIN OUTCOMES AND MEASURES
Primary outcomes included body weight, BMI, waist circumference, blood pressure, medication use, cognitive performance (20% change index of compound z-score), brain volumes, cortical thickness, cerebral blood flow (CBF), and spatial coefficient of variation (sCOV). Secondary outcomes include cytokines, adipokines, depressive symptoms (assessed using the Beck Depression Inventory), and physical activity (assessed using the Baecke Questionnaire).
RESULTS
A total of 133 participants (mean [SD] age, 46.8 [5.7] years; 112 [84.2%] female) were included. Global cognition was at least 20% higher in 52 participants (42.9%) at 24 months after BS. Compared with baseline, at 24 months, inflammatory markers were lower (mean [SD] high-sensitivity C-reactive protein: 4.77 [5.80] μg/mL vs 0.80 [1.09] μg/mL; P < .001), fewer patients used antihypertensives (48 patients [36.1%] vs 22 patients [16.7%]), and patients had lower depressive symptoms (median [IQR] BDI score: 9.0 [5.0-13.0] vs 3.0 [1.0-6.0]; P < .001) and greater physical activity (mean [SD] Baecke score: 7.64 [1.29] vs 8.19 [1.35]; P < .001). After BS, brain structure and perfusion were lower in most brain regions, while hippocampal and white matter volume remained stable. CBF and sCOV did not change in nucleus accumbens and parietal cortex. The temporal cortex showed a greater thickness (mean [SD] thickness: 2.724 [0.101] mm vs 2.761 [0.007] mm; P = .007) and lower sCOV (median [IQR] sCOV: 4.41% [3.83%-5.18%] vs 3.97% [3.71%-4.59%]; P = .02) after BS.
CONCLUSIONS AND RELEVANCE
These findings suggest that BS was associated with health benefits 2 years after surgery. BS was associated with improved cognition and general health and changed blood vessel efficiency and cortical thickness of the temporal cortex. These results may improve treatment options for patients with obesity and dementia.
Topics: Humans; Female; Middle Aged; Male; Cohort Studies; Bariatric Surgery; Obesity; Cognition; Brain; Weight Loss
PubMed: 38334996
DOI: 10.1001/jamanetworkopen.2023.55380 -
Schizophrenia Bulletin Nov 2023Schizophrenia is a multidimensional disease. This study proposes a new research framework that combines multimodal meta-analysis and genetic/molecular architecture to... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND HYPOTHESIS
Schizophrenia is a multidimensional disease. This study proposes a new research framework that combines multimodal meta-analysis and genetic/molecular architecture to solve the consistency in neuroimaging biomarkers of schizophrenia and whether these link to molecular genetics.
STUDY DESIGN
We systematically searched Web of Science, PubMed, and BrainMap for the amplitude of low-frequency fluctuations (ALFF) or fractional ALFF, regional homogeneity, regional cerebral blood flow, and voxel-based morphometry analysis studies investigating schizophrenia. The pooled-modality, single-modality, and illness duration-dependent meta-analyses were performed using the activation likelihood estimation algorithm. Subsequently, Spearman correlation and partial least squares regression analyses were conducted to assess the relationship between identified reliable convergent patterns of multimodality and neurotransmitter/transcriptome, using prior molecular imaging and brain-wide gene expression.
STUDY RESULTS
In total, 203 experiments comprising 10 613 patients and 10 461 healthy controls were included. Multimodal meta-analysis showed that brain regions of significant convergence in schizophrenia were mainly distributed in the frontotemporal cortex, anterior cingulate cortex, insula, thalamus, striatum, and hippocampus. Interestingly, the analyses of illness-duration subgroups identified aberrant functional and structural evolutionary patterns: Lines from the striatum to the cortical core networks to extensive cortical and subcortical regions. Subsequently, we found that these robust multimodal neuroimaging abnormalities were associated with multiple neurobiological abnormalities, such as dopaminergic, glutamatergic, serotonergic, and GABAergic systems.
CONCLUSIONS
This work links transcriptome/neurotransmitters with reliable structural and functional signatures of brain abnormalities underlying disease effects in schizophrenia, which provides novel insight into the understanding of schizophrenia pathophysiology and targeted treatments.
Topics: Humans; Schizophrenia; Magnetic Resonance Imaging; Transcriptome; Brain; Neuroimaging
PubMed: 37607339
DOI: 10.1093/schbul/sbad047 -
Journal of Clinical Laboratory Analysis Nov 2023Adrenocortical carcinoma (ACC) is an aggressive and rare malignant tumor associated with poor outcomes. Cuproptosis, a new pattern of cell death, relies on mitochondrial...
BACKGROUND
Adrenocortical carcinoma (ACC) is an aggressive and rare malignant tumor associated with poor outcomes. Cuproptosis, a new pattern of cell death, relies on mitochondrial respiration and is associated with protein lipoylation. Increasing evidence has demonstrated the potential roles of cuproptosis in several tumor entities. However, the relationship between cuproptosis and ACC remains unclear.
METHODS
In total, 10 cuproptosis-related genes (CRGs) of patients with ACC were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases and differential expression analysis of CRGs was analyzed. Functional enrichment of the CRGs was performed and protein-protein interaction analysis was utilized to explore the association between the CRGs. Cuproptosis-related risk score (CRRS) was constructed by Lasso Cox regression and validated.
RESULTS
In the current study, the alteration and expression patterns of 10 CRGs in TCGA-ACC datasets were analyzed. We identified different expression patterns of CRGs in ACCs, discovered strong associations between CRGs and ACCs, and found that the CRGs were associated with immune infiltration in ACCs. A CRRS was created thereafter to predict overall survival (OS). CRRS = (0.083103718) *FDX1 + (-0.278423862) *LIAS+(0.090985682) *DLAT+(-0.018784047) *PDHA1 + (0.297218951) *MTF1 + (0.310197964) *CDKN2A. Patients were divided into high- and low-risk groups based on their CRRS, and independent prognostic factors were investigated. Finally, CDKN2A and FDX1 were found to be independent prognostic predictors of patients with ACC.
CONCLUSIONS
CDKN2A and FDX1 are independent prognostic predictors of patients with ACC. Cuproptosis may play a role in the development of ACC, providing a new perspective on therapeutic strategies related to CRGs for cancer prevention and treatment.
Topics: Humans; Prognosis; Adrenocortical Carcinoma; Agenesis of Corpus Callosum; Databases, Factual; Adrenal Cortex Neoplasms; Apoptosis; Copper
PubMed: 37997497
DOI: 10.1002/jcla.24981 -
Frontiers in Public Health 2023Different medication prescription patterns have been associated with varying course of disease and outcomes in COVID-19. Health claims data is a rich source of...
BACKGROUND
Different medication prescription patterns have been associated with varying course of disease and outcomes in COVID-19. Health claims data is a rich source of information on disease treatment and outcomes. We aimed to investigate drug prescription patterns and their association with mortality and hospitalization via insurance data for a relatively long period of the pandemic in Iran.
METHODS
We retrieved hospitalized patients' data from Iran Health Insurance Organization (IHIO) spanning 26 months (2020-2022) nationwide. Included were patients with ICD-10 codes U07.1/U07.2 for confirmed/suspected COVID-19. A case was defined as a single hospitalization event for an individual patient. Multiple hospitalizations of a patient within a 30-day interval were aggregated into a single case, while hospitalizations with intervals exceeding 30 days were treated as independent cases. The Anatomical Therapeutic Chemical (ATC) was used for medications classification. The two main study outcomes were general and intensive care unit (ICU) hospitalization periods and mortality. Besides, various demographic and clinical associate factors were analyzed to derive the associations with medication prescription patterns and study outcomes using accelerated failure time (AFT) and logistic regression models.
RESULTS
During the 26 months of the study period, 1,113,678 admissions with COVID-19 diagnosis at hospitals working in company with IHIO were recorded. 917,198 cases were detected from the database, among which 51.91% were females and 48.09% were males. Among the main groups of medications, antithrombotics (55.84% [95% CI: 55.74-55.94]), corticosteroids (54.14% [54.04-54.24]), and antibiotics (42.22% [42.12-42.32]) were the top used medications among cases with COVID-19. Investigation of the duration of hospitalization based on main medication groups showed antithrombotics (adjusted median ratio = 0.94 [0.94-0.95]) were significantly associated with shorter periods of overall hospitalization. Also, antithrombotics (adjusted odds ratio = 0.74 [95%CI, 0.73-0.76]), corticosteroids (0.97 [0.95-0.99]), antivirals (0.82 [0.80-0.83]), and ACE inhibitor/ARB (0.79 [0.77-0.80]) were significantly associated with lower mortality.
CONCLUSION
Over 2 years of investigation, antithrombotics, corticosteroids, and antibiotics were the top medications for hospitalized patients with COVID-19. Trends in medication prescription varied based on various factors across the country. Medication prescriptions could potentially significantly impact the trends of mortality and hospitalization during epidemics, thereby affecting both health and economic burdens.
Topics: Male; Female; Humans; COVID-19; Angiotensin Receptor Antagonists; Big Data; COVID-19 Testing; Fibrinolytic Agents; Angiotensin-Converting Enzyme Inhibitors; Hospitalization; Drug Prescriptions; Adrenal Cortex Hormones; Anti-Bacterial Agents
PubMed: 38164450
DOI: 10.3389/fpubh.2023.1280434 -
Aging and Disease Nov 2023Type 2 diabetes mellitus (T2DM) increases the risk of neurological diseases, yet how brain oscillations change as age and T2DM interact is not well characterized. To...
Type 2 diabetes mellitus (T2DM) increases the risk of neurological diseases, yet how brain oscillations change as age and T2DM interact is not well characterized. To delineate the age and diabetic effect on neurophysiology, we recorded local field potentials with multichannel electrodes spanning the somatosensory cortex and hippocampus (HPC) under urethane anesthesia in diabetic and normoglycemic control mice, at 200 and 400 days of age. We analyzed the signal power of brain oscillations, brain state, sharp wave associate ripples (SPW-Rs), and functional connectivity between the cortex and HPC. We found that while both age and T2DM were correlated with a breakdown in long-range functional connectivity and reduced neurogenesis in the dentate gyrus and subventricular zone, T2DM further slowed brain oscillations and reduced theta-gamma coupling. Age and T2DM also prolonged the duration of SPW-Rs and increased gamma power during SPW-R phase. Our results have identified potential electrophysiological substrates of hippocampal changes associated with T2DM and age. The perturbed brain oscillation features and diminished neurogenesis may underlie T2DM-accelerated cognitive impairment.
PubMed: 38029397
DOI: 10.14336/AD.2023.1106 -
NeuroImage Dec 2023Literature suggests that attention is a critical cognitive process for pain perception and modulation and may play an important role in placebo and nocebo effects. Here,... (Randomized Controlled Trial)
Randomized Controlled Trial
Modulation effects of repeated transcranial direct current stimulation on the dorsal attention and frontal parietal networks and its association with placebo and nocebo effects.
Literature suggests that attention is a critical cognitive process for pain perception and modulation and may play an important role in placebo and nocebo effects. Here, we investigated how repeated transcranial direct current stimulation (tDCS) applied at the dorsolateral prefrontal cortex (DLPFC) for three consecutive days can modulate the brain functional connectivity (FC) of two networks involved in cognitive control: the frontoparietal network (FPN) and dorsal attention network (DAN), and its association with placebo and nocebo effects. 81 healthy subjects were randomized to three groups: anodal, cathodal, and sham tDCS. Resting state fMRI scans were acquired pre- and post- tDCS on the first and third day of tDCS. An Independent Component Analysis (ICA) was performed to identify the FPN and DAN. ANCOVA was applied for group analysis. Compared to sham tDCS, 1) both cathodal and anodal tDCS increased the FC between the DAN and right parietal operculum; cathodal tDCS also increased the FC between the DAN and right postcentral gyrus; 2) anodal tDCS led to an increased FC between the FPN and right parietal operculum, while cathodal tDCS was associated with increased FC between the FPN and left superior parietal lobule/precuneus; 3) the FC increase between the DAN and right parietal operculum was significantly correlated to the placebo analgesia effect in the cathodal group. Our findings suggest that both repeated cathodal and anodal tDCS could modulate the FC of two important cognitive brain networks (DAN and FPN), which may modulate placebo / nocebo effects.
Topics: Humans; Transcranial Direct Current Stimulation; Nocebo Effect; Prefrontal Cortex; Brain; Pain
PubMed: 37939891
DOI: 10.1016/j.neuroimage.2023.120433